N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-3-carboximidoyl chloride, along with several related compounds, is known from WO 97/16439 as an effective agent suitable for increasing the chaperone expression of cells. In this publication, the compound is defined as a novel compound, and the N-oxide derivatives of the compound are also claimed, but there is no specific mention of the N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride, and its preparation process is not described either.
N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride is disclosed and claimed as a novel compound in WO 00/50403, and its production process is described there as well. The compound is produced by the oxidation of the N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-3-carboximidoyl chloride. In the course of oxidation with peracids, the bis-N-oxide derivative oxidized on the N-atoms of both the piperidine ring and the pyridine ring, or the piperidine-N-oxide derivative are formed preferentially, and therefore the oxidation with peracid must be performed in the presence of a strong acid to ensure the dominance of the formation of the pyridine-N-oxide derivative in the course of the oxidation process. The yield of this process, however, is not satisfactory. The optically active enantiomers of the N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximid-oyl chloride are also described in WO 00/50403. They are prepared in a way similar to the preparation of the raceme compound using the suitable optically active starting substances.
Considering the fact that the N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride and its optically active enantiomers are not only useful in the treatment of diabetic complications, primarily retinopathy, neuropathy and nephropathy, but simultaneously reduce chronic insulin resistance, these compounds are valuable active ingredients in pharmaceutical products. However, in order for these compounds to be useful in the pharmaceutical industry, an easier process is necessary for their production.